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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation, other
Remarks:
in vivo study performed prior to change in information requirements
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
of 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
of 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
of 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese MAFF Test Data for Registration of Agricultural Chemicals, Eye Irritation (2-1-5), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000.
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Stock supply of healthy adult rabbits
- Number and Sex: 3 females
- Age on day of dosing (Day 1): 40 or 41 weeks
- Weight prior to dosing (Day 1): Minimum 3.97 kg, maximum 4.09 kg
- Housing: Individual housing in plastic cages with peforated floor
- Environmental enrichment: Small soft white untreated wood blocks
- Diet : Standard laboratory rabbit diet (125 g/animal/day). In addition, dietary supplement of hay
replaced by a supplement of wholemeal bread as from 2 days prior to dose instillation.
- Water: Drinking water, ad libitum
- Acclimation period: 29 or 30 weeks prior to study start under laboratory conditions.

Routine analysis of the batch of diet used for nutrients, possible contaminants and microorganisms and of the drinking water were conducted or available at the testing facility.


ENVIRONMENTAL CONDITIONS

Air conditioned animal room set at:
- Temperature (°C): 18 ± 2°C
- Relative Humidity (%): 40 to 70%
- Photoperiod: 12 hrs artificial light per 24 hrs

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL of undiluted liquid test substance was administered into the conjunctival sac of one eye per rabbit (right eye). The contralateral eye (left eye) remained untreated to serve as a control.
Duration of treatment / exposure:
The eyes were not rinsed after treatment. Therefore, the treatment/exposure period was equivalent to the entire observation period following instillation or lasted until removal of the test material by physiological mechanisms, whichever happened sooner.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 adult female rabbits
Details on study design:
EYE EVALUATION:

Before treatment start both eyes of each animal were investigated to ensure that there was no pre-existing corneal damage, iridial inflammation or conjunctival irritation.

One animal (the sentinel) was initially treated and in the absence of a severe effect the remaining two animals were committed to the study.

Eyes were evaluated in all animals at approximately 1, 24, 48 and 72 hours after test substance instillation adopting the numerical scoring system listed in Table 1 in the field below. Grades attained at 24, 48 and 72 hours after instillation were included in the mean gradings of ocular lesions and used for evaluation of the necessity of eye irritation/corrosion classification. As from 24 h after test substance instillation, staining with fluorescein supported the recognition of corneal lesions in female #3.

Equipment used for eye evaluation: Ophthalmoscope or pencil beam torch

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: Corneal ulceration or opacity were not evident
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: Corneal ulceration or opacity were not evident
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
other: Iridic changes were not evident
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
other: Iridic changes were not evident
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
1.4
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0.9
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: Discharge
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
other: 24, 48, 72 h
Score:
0.9
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: Discharge
Basis:
animal #1
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
other: Discharge
Basis:
animal #2
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: on one occasion mucoid
Irritation parameter:
other: Discharge
Basis:
animal #3
Remarks:
mean over 3 time points
Time point:
other: 24, 48, 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: at times mucoid
Irritant / corrosive response data:
In one animal (#1) ocular lesions were confined to conjunctival redness at 1, 24 and 48 hours after test substance instillation associated with chemosis and discharge at 1 hour after instillation. All of these findings were grade 1 and fully reversible. These findings were also evident in another animal (#2), but at higher severity (up to grade 2) and persisting slightly longer. In addition to conjunctival redness, chemosis and discharge, each up to grade 2, corneal opacity up to grade 2 and iritis grade 1 were recorded in the third animal (#3) all findings being reversible, as by 14 days after instillation also this animal was entirely free from ocular lesions.
Other effects:
Observation of the animals for defined behavioural criteria led to the conclusion that instillation of the test substance induced practically no initial pain response. Any other signs of systemic toxicity or ill health were not evident.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The outcome of the present in vivo study does not necessitate any labelling regarding eye irritation according to EU classification rules [DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008]. The findings noted were fully reversible and their incidence is within the category “not irritating to eyes”.